DESCRIPTION: Heterotrimeric guanine nucleotide-binding regulatory proteins (G-proteins) form a large family of signaling proteins that are involved in transitory interactions with membrane bound receptors. The subunits in heterotrimeric G-proteins are designated a (Mr 40-46 KDa), b (Mr 37 KDa), and g (Mr 8 KDa); the G-protein a subunit contains GTPase activity. The Gabg-GDP is the basal complex state and, upon an appropriate signal, GDP is released and the dissociated species Ga-GTP and bg transduces the signal downstream. After GTP hydrolysis, the Gabg-GDP is reformed and the signal is terminated. The principal investigator's group has determined the structures of several Gia species including Gia1-GDP, Gia1b1g2, and Gia1-ligand complexes. The principal investigator proposes to continue his group's studies into the structural and functional consequences of GTP hydrolysis on the Ga-GTP species, particularly in the context of signal transduction, as well as determine the structures of Gia1 complexes with RGS4 or GIAP and the structure of Gsa complexed with a adenyl cyclase core fragment..